Silver has long been established as having effective antimicrobial activity attributable to the oligodynamic effect where metal ions have a toxic effect on bacteria. Although the exact mechanism of toxicity is still uncertain, evidence suggests that silver ions denature enzymes of the target organism by binding to reactive groups and interfering with their metabolism.
Silver also has low toxicity in the human body and poses little risk when inhaled, ingested or applied to the skin and is used as an antimicrobial agent in a wide variety of applications including for example, incorporation into wound dressings. Such antimicrobial agents are often mixed with highly absorbent materials which collect the wound exudate. Silver is also used in creams, as an antibiotic coating on medical devices such as endotracheal tubes to reduce ventilator associated pneumonia and urinary catheters to reduce urinary tract infections. Silver is also employed as a water purification agent, for example within hospitals that filter hot water through copper and silver filters to decrease the risk of MRSA and legionella infections.
Other metals such as copper and its alloys are natural antimicrobial materials and control a wide range of moulds, fungi, algae and harmful microbes. Although the nature of the antimicrobial mechanism is uncertain, evidence suggests that elevated copper levels inside a cell causes oxidative stress, a decline in the membrane integrity and inappropriate binding to proteins which do not require copper for their function. Various studies have been conducted to investigate the antibacterial properties of copper touch surfaces, which may be introduced to door handles in hospitals to reduce the transmission of infection. Copper touch surfaces have been shown to significantly reduce the number of viable microbes such as Escherichia Coli, Methicillin-Resistant Staphylococcus Aureus (MRSA), Clostridium difficile, Influenza A and Adenovirus.
Zinc represents a further antimicrobial agent and is of biological importance exhibiting significant antimicrobial properties even at low concentrations. Zinc is commonly incorporated within topical ointments to protect against sunburn and is used in toothpaste to prevent halitosis and anti-dandruff shampoos. Zinc oxide nanoparticles have also been used within the linings of food cans and in packages of meat to extend shelf-life. Other metals also exhibit antimicrobial effects include gold, platinum, palladium, bismuth, tin and antimony.
There has been significant interest in incorporating such anti-microbial agents into wound dressings with the aim of releasing the antimicrobial agents into the wound site and promoting healing. Managing the wound environment and in particular wound exudate (produced as part of the healing process), is a constant challenge for healthcare professionals. The exudate plays several important roles in promoting healing, for example maintaining a moist environment necessary for cellular activity and carrying white blood cells to where they are most needed. Wound exudate is rich in leucocytes, proteases and growth factors which all work together to clear debris from the wound and promote new growth of tissue. While it is important to keep the wound moist, an overly wet environment may damage the wound bed. Therefore, effective management is needed by the application of wound dressings.
Alginates are often used as highly absorbent fibres to collect the wound exudate and by incorporating antimicrobial agents into the fibres, upon absorption of the wound exudate, ion-exchange takes place and releases the antimicrobial agent to assist in wound healing. A biofilm layer is often formed by wound bacteria as a defense against antimicrobials or adverse environmental factors, and can be difficult to breakdown, creating problems with delivering the target antimicrobial agents to the active site.
U.S. Pat. No. 5,888,526 describes that metal salts of organic compounds incorporated into fibrous material to inhibit mould and bacteria. In particular, Ag, Cu and Zn in combination with organic compounds such as pyrrole, pyrimidine, imidazole and thiazole are employed.
WO 2011/160862 is concerned with wound bandages for treatment of purulent and for prevention of suppurations of infected wounds. A nanostructured powder of bentonite intercalated by metal ions such as Ag, Cu and Zn is incorporated into a textile carrier for use as a wound dressing.
WO 2012/098298 discloses a non-woven fabric formed as a blend of at least two different fibre types. A first fibre is coated with elemental silver and a second fibre is essentially free from silver to provide mechanical strength. The fibres are bonded together by hydroentanglement.
US 2006/0149182 describes wound dressing materials comprising complexes of anionic polysaccharides with silver combined with a hydrocolloid adhesive. The dressing optionally incorporates other antimicrobial metal ions such as Bi, Cu, Ni, Zn, Mn, Mg and Au. The metallic ions may be maintained within compounds such as zeolite and hydroxyl apatite.
US 2008/0299160 explains a method of manufacture of polymer composites which incorporate metal nanoparticles for antimicrobial wound dressings.
US 2007/0275043 describes a wound contacting material incorporating a silver salt for delivering silver to a wound. The wound contacting material may take a number of forms, for example, alginate, chitosan, viscose, polyester, polyamide, polyethylene and polypropylene. In other embodiments, the material may also be selected from a foam or amorphous gel or collagen material. Alginate is preferred as an absorbent material for use in wound dressings to absorb wound exudate. Other water soluble polysaccharides may also be added to the material such as CMC, HPMC, pectin and other similar species and derivatives.
Fibres for use in the manufacture of wound dressings have been created using the well-established fibre spinning process that is a form of extrusion where a spinneret forms multiple continuous filaments which are then drawn to form a fibre. Four types of spinning methods are traditionally used for creating fibres: wet, dry, melt and gel.
The process of wet spinning involves the polymer being dissolved into a dope solution which is then forced under pressure through the spinneret submerged in a chemical coagulation bath. The filaments precipitate out of solution and are then drawn to form a fibre. Acrylic, rayon and spandex fibres are produced by this process. Dry spinning involves a similar process to wet spinning except the fibre is solidified through evaporation of the solvent and not coagulation. Melt spinning involves using polymers which do not require dissolution and are merely melted with the resulting fibre solidified on cooling. Gel spinning is a combination of wet and dry spinning and is often used to obtain high strength fibres. The polymer exists in a gel-like state which keeps the polymer chains partially bound together.
Metals in the form of salts or nanoparticles can be incorporated into such fibres in wet spinning by incorporating them in the dope solution or coagulation bath. However, there are often substantial problems associated with such techniques, including low solubility of the metal compounds in aqueous solution and displacement and precipitation reactions.
In particular, silver is typically incorporated in the dope solution, but this is often difficult due to the low solubility of silver compounds in aqueous solution. Some of the silver compound may not be fully incorporated into solution and the dope must be filtered in order to remove any precipitate before spinning can begin. As the spinneret is made from a series of small holes, clogging with precipitate during the spinning process is a particular problem. Accordingly, incorporating silver ions into a fibre using such spinning methodology is often expensive, inefficient and wasteful. Additionally, the efficiency of the spinning process is also largely dependent on the viscosity of the dope solution and at lower viscosity, the process is much more effective as the dope may pass through the spinneret with greater ease. This places an efficiency restraint on existing approaches that are not optimised in this respect.